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Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.

ABSTRACT: RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform (KRAS, HRAS, and NRAS), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS-targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele-specific inhibitors against KRAS^G12C . Targeting the remaining RAS mutants would require further experimental elucidation of RAS signal transduction, RAS-altered metabolism, and the associated immune microenvironment. This study reviews the mechanisms and efficacy of novel targeted therapies for different RAS mutants, including KRAS allele-specific inhibitors, combination therapies, immunotherapies, and metabolism-associated therapies.

SUBMITTER: Yang H

PROVIDER: S-EPMC9859734 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Targeting RAS mutants in malignancies: successes, failures, and reasons for hope.

Yang Hang H Zhou Xinyi X Fu Dongliang D Le Chenqin C Wang Jiafeng J Zhou Quan Q Liu Xiangrui X Yuan Ying Y Ding Kefeng K Xiao Qian Q

Cancer communications (London, England) 20221031 1

RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform (KRAS, HRAS, and NRAS), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS-targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele-specific inhibitors against KRAS<sup>G12C</sup> . Targeting the remaining RAS mutants would require further experimen ...[more]

PMID: 36316602

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